Cell suicide gets out of control.

One of the hottest topics in biology is apoptosis, the phenomenon in which a cell kills itself through a series of carefully choreographed actions (SN: 11/21/92, p. 344; 1/15/94, p. 44). Often referred to as cellular suicide, apoptosis is a widely used natural mechanism that organisms employ to eliminate damaged, aged, or unneeded cells.

Several diseases may result from apoptosis gone awry. Autoimmune lymphoproliferative syndrome, a disorder marked by rashes, enlarged lymph nodes, and sometimes kidney damage, apparently stems from immune cells that persist too long after they have fought off an infection. Normally, "when the war is over, it's time for the troops to disarm and go away," says Jennifer M. Puck of the National Center for Human Genome Research in Bethesda, Md.

Puck and her colleagues have examined eight children with the autoimmune disorder and found that all possess mutations in the Fas gene. Fas codes for a cell surface protein that enables cells to receive specific commands to undergo apoptosis. The mutations in Fas apparently prevent unneeded immune cells from properly receiving this suicide signal, thereby triggering the autoimmune disease, says Puck.

Apoptosis may also play a role in amyotrophic lateral sclerosis (ALS), the neurodegenerative disorder better known as Lou Gehrig's disease. In 1993, researchers found that an inherited form of ALS results from mutations in an enzyme called superoxide dismutase (SN: 3/6/93, p. 148). The enzyme seems to protect cells from damage by reactive molecules called free radicals. Dale E. Bredesen of the Burnham Institute in La Jolla, Calif., and his colleagues now find that the mutant forms of superoxide dismutase trigger nerve cells to commit suicide. The normal enzyme protects cells from apoptosis, says Bredesen.

Apoptosis is a suspect in other neurodegenerative diseases as well, including Alzheimer's and Huntington's diseases. Scientists have just discovered, for example, that an enzyme involved in apoptosis interacts with huntingtin, the protein that causes Huntington's disease. That apoptosis enzyme, apopain, cleaves disease-causing forms of huntingtin much more efficiently than normal forms, reports a research group headed by Michael Hayden of the University of British Columbia in Vancouver. The change may cause the abnormal brain cell death seen in the disease, the investigators speculate.